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Safety Tolerability and Efficacy of Intravitreal LMG324 in the Treatment of Neovascular Age-Related Macular Degeneration

Primary Purpose

Age-related Macular Degeneration (AMD)

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

LMG324

Ranibizumab 0.5 mg

Sham

About this trial

This is an interventional treatment trial for Age-related Macular Degeneration (AMD) focused on measuring First-in-human, anti-VEGF, neovascular AMD (nvAMD)

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Must give written informed consent, be able to make the required study visits and follow instructions.
Best corrected visual acuity (BCVA) of 34 letters (approximately 20/200 Snellen or better) in the non-study eye.

SAD population only:

Subject's study eye must have a choroidal neovascularization (CNV) lesion due to age-related macular degeneration (AMD), either treatment naïve or previously treated, that can be expected to benefit, in the opinion of the investigator, from anti-vascular endothelial growth factor (anti-VEGF) therapy.
Previously treated eyes must have a history of least 3 administrations of any intravitreal (IVT) anti-VEGF therapeutic for the treatment of CNV with the last injection administered ≥ 1 month prior to the planned administration of the study drug.

Enrollment expansion population only

Subject's study eye must have untreated and active CNV lesion due to AMD.
BCVA, between 73 - 23 letters, inclusive (approximate Snellen equivalent 20/40 - 20/320) in the study eye.

Exclusion Criteria:

SAD and enrollment expansion population

Both eyes: any active ocular or periocular infection or active intraocular inflammation (eg, infectious blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis).
Study eye: current vitreous hemorrhage or a history of rhegmatogenous retinal detachment.
Study eye: uncontrolled glaucoma (intraocular pressure [IOP] >25 mmHg on medication or according to Investigator's judgment).

SAD population only

Presence of any contraindications, in the Investigator's opinion, to IVT anti-VEGF therapeutic administration.

Enrollment expansion population only

Study eye: subject has received any approved or investigational treatment for exudative (wet) AMD other than vitamin supplements.
Study eye: any current or history of macular or retinal disease other than exudative AMD
Study eye: serous pigment epithelial detachment (PED) under the foveal center or retinal pigment epithelium (RPE) tear/rip.
Study eye: any concurrent intraocular condition (eg, cataract, diabetic retinopathy) that, in the opinion of the Investigator, could either require medical or surgical intervention during the course of the study.
Study eye: other ocular diseases that, in the opinion of the Investigator, can compromise the visual acuity
Study eye: Surgery, as specified in the protocol.

Sites / Locations

Call Alcon Call Center for Trial Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

LMG324

LMG324 + sham

Lucentis + sham

Arm Description

SAD: LMG324 administered as a single IVT injection in 1 eye (study eye) in 1 of 4 doses, with 15-day follow-up

Expansion: LMG324 administered as a single IVT injection in 1 eye (study eye), followed by sham injections, until implementation of SoC therapy as specified in the protocol, for 24 weeks

Expansion: Ranibizumab 0.5 mg administered as monthly IVT injections in 1 eye (study eye) with interim sham injections, for 24 weeks

Outcomes

Primary Outcome Measures

Mean change from baseline in best corrected visual acuity (BCVA) at Day 85

Secondary Outcome Measures

Percentage of LMG324-treated subjects with no identified SoC treatment need up to and including Day 85

Best Corrected Visual Acuity (BCVA)

Central subfield thickness total (CSFTtot)

Central subfield thickness neuro-retina (CFSTnr)

Lesion thickness

Subretinal fluid with foveal involvement (SRFfi) thickness

Retinal pigment epithelial detachment with foveal involvement (PEDfi) thickness

Area of lesion (associated with CNV)

Area of CNV within a lesion

Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t)

Maximum observed maximum plasma concentration (Cmax)

Time to reach the maximum observed plasma concentration (Tmax)

Observed maximum plasma concentration following drug administration, by dose (Cmax/D)

Area under the plasma concentration-time curve divided by dose (AUC/D)

Frequency of subjects with anti-LMG324 antibodies

Full Information

NCT ID

NCT02398500

First Posted

March 20, 2015

Last Updated

June 3, 2019

Sponsor

Alcon Research

Collaborators

Novartis Institutes for BioMedical Research

1. Study Identification

Unique Protocol Identification Number

NCT02398500

Brief Title

Safety Tolerability and Efficacy of Intravitreal LMG324 in the Treatment of Neovascular Age-Related Macular Degeneration

Official Title

An Open-label Single Ascending Dose and Randomized Double-Masked, Ranibizumab Controlled, Safety, Tolerability, and Efficacy Study of Intravitreal LMG324 in Subjects With Neovascular Age-Related Macular Degeneration

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Terminated

Why Stopped

Management decision

Study Start Date

July 22, 2015 (Actual)

Primary Completion Date

February 29, 2016 (Actual)

Study Completion Date

May 20, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alcon Research

Collaborators

Novartis Institutes for BioMedical Research

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this first-in-human study is to evaluate the safety and tolerability of single ascending doses of LMG324 to determine the maximum tolerated dose (MTD) in neovascular age-related macular degeneration (nvAMD) subjects. Enrollment will be expanded at a safe and tolerated dose in treatment naïve nvAMD subjects to compare a single intravitreal (IVT) dose of LMG324 to ranibizumab 0.5 mg administered every 4 weeks for change from baseline in best-corrected visual acuity (BCVA) at Week 12 (Day 85).

Detailed Description

The study will start with a single dose ascending (SAD) phase. LMG324 will be administered on Day 1 with no further treatment until implementation of standard of care (SoC) therapy. SoC therapy is ranibizumab 0.5 mg administered per label. Dose groups will be implemented sequentially to allow for safety review between the current and subsequent dose group. All treatments will be open-label, including ranibizumab used as SoC therapy. In the enrollment expansion phase, subjects randomized to LMG324 arm will receive a single LMG324 IVT injection on Day 1 followed by sham (fake) IVT injections until implementation of SoC therapy. After implementation, SoC therapy will be applied monthly with sham injections applied at the interim planned visits. The enrollment expansion phase may start at a selected dose level whilst the dose escalation phase is still ongoing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Age-related Macular Degeneration (AMD)

Keywords

First-in-human, anti-VEGF, neovascular AMD (nvAMD)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LMG324

Arm Type

Experimental

Arm Description

SAD: LMG324 administered as a single IVT injection in 1 eye (study eye) in 1 of 4 doses, with 15-day follow-up

Arm Title

LMG324 + sham

Arm Type

Experimental

Arm Description

Expansion: LMG324 administered as a single IVT injection in 1 eye (study eye), followed by sham injections, until implementation of SoC therapy as specified in the protocol, for 24 weeks

Arm Title

Lucentis + sham

Arm Type

Active Comparator

Arm Description

Expansion: Ranibizumab 0.5 mg administered as monthly IVT injections in 1 eye (study eye) with interim sham injections, for 24 weeks

Intervention Type

Biological

Intervention Name(s)

LMG324

Intervention Description

IVT injection

Intervention Type

Biological

Intervention Name(s)

Ranibizumab 0.5 mg

Other Intervention Name(s)

Lucentis®

Intervention Description

IVT injection

Intervention Type

Biological

Intervention Name(s)

Sham

Intervention Description

Fake injection used for masking purposes

Primary Outcome Measure Information:

Title

Mean change from baseline in best corrected visual acuity (BCVA) at Day 85

Time Frame

Baseline, Day 85

Secondary Outcome Measure Information:

Title

Percentage of LMG324-treated subjects with no identified SoC treatment need up to and including Day 85

Time Frame

Up to Day 85

Title

Best Corrected Visual Acuity (BCVA)

Time Frame

Up to Day 169

Title

Central subfield thickness total (CSFTtot)

Time Frame

Up to Day 169

Title

Central subfield thickness neuro-retina (CFSTnr)

Time Frame

Up to Day 169

Title

Lesion thickness

Time Frame

Up to Day 169

Title

Subretinal fluid with foveal involvement (SRFfi) thickness

Time Frame

Up to Day 169

Title

Retinal pigment epithelial detachment with foveal involvement (PEDfi) thickness

Time Frame

Up to Day 169

Title

Area of lesion (associated with CNV)

Time Frame

Up to Day 169

Title

Area of CNV within a lesion

Time Frame

Up to Day 169

Title

Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

Time Frame

Up to Day 169

Title

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

Time Frame

Up to Day 169

Title

Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t)

Time Frame

Up to Day 169

Title

Maximum observed maximum plasma concentration (Cmax)

Time Frame

Up to Day 169

Title

Time to reach the maximum observed plasma concentration (Tmax)

Time Frame

Up to Day 169

Title

Observed maximum plasma concentration following drug administration, by dose (Cmax/D)

Time Frame

Up to Day 169

Title

Area under the plasma concentration-time curve divided by dose (AUC/D)

Time Frame

Up to Day 169

Title

Frequency of subjects with anti-LMG324 antibodies

Time Frame

Up to Day 169

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Must give written informed consent, be able to make the required study visits and follow instructions. Best corrected visual acuity (BCVA) of 34 letters (approximately 20/200 Snellen or better) in the non-study eye. SAD population only: Subject's study eye must have a choroidal neovascularization (CNV) lesion due to age-related macular degeneration (AMD), either treatment naïve or previously treated, that can be expected to benefit, in the opinion of the investigator, from anti-vascular endothelial growth factor (anti-VEGF) therapy. Previously treated eyes must have a history of least 3 administrations of any intravitreal (IVT) anti-VEGF therapeutic for the treatment of CNV with the last injection administered ≥ 1 month prior to the planned administration of the study drug. Enrollment expansion population only Subject's study eye must have untreated and active CNV lesion due to AMD. BCVA, between 73 - 23 letters, inclusive (approximate Snellen equivalent 20/40 - 20/320) in the study eye. Exclusion Criteria: SAD and enrollment expansion population Both eyes: any active ocular or periocular infection or active intraocular inflammation (eg, infectious blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis). Study eye: current vitreous hemorrhage or a history of rhegmatogenous retinal detachment. Study eye: uncontrolled glaucoma (intraocular pressure [IOP] >25 mmHg on medication or according to Investigator's judgment). SAD population only Presence of any contraindications, in the Investigator's opinion, to IVT anti-VEGF therapeutic administration. Enrollment expansion population only Study eye: subject has received any approved or investigational treatment for exudative (wet) AMD other than vitamin supplements. Study eye: any current or history of macular or retinal disease other than exudative AMD Study eye: serous pigment epithelial detachment (PED) under the foveal center or retinal pigment epithelium (RPE) tear/rip. Study eye: any concurrent intraocular condition (eg, cataract, diabetic retinopathy) that, in the opinion of the Investigator, could either require medical or surgical intervention during the course of the study. Study eye: other ocular diseases that, in the opinion of the Investigator, can compromise the visual acuity Study eye: Surgery, as specified in the protocol.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Scientist I, NIBR

Organizational Affiliation

Alcon Research

Official's Role

Study Director

Facility Information:

Facility Name

Call Alcon Call Center for Trial Locations

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76134

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Safety Tolerability and Efficacy of Intravitreal LMG324 in the Treatment of Neovascular Age-Related Macular Degeneration

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